FDA Approves Adquey (difamilast 1%) Ointment for the Treatment of Mild-to-Moderate Atopic Dermatitis

Acrotech Biopharma Inc., a bio-pharmaceutical company focused on developing and commercializing innovative propriety medications, in collaboration with Otsuka Pharmaceutical Co., Ltd.,  announced  the U.S. Food and Drug Administration (FDA) approval of  New Drug Application (NDA) for Adquey (difamilast 1%) ointment, for the topical treatment of mild-to-moderate atopic dermatitis (AD) in adults and pediatric patients aged 2 and older.

Adquey is a novel, non-steroidal, topical phosphodiesterase 4 (PDE4) inhibitor. This approval provides a new non-steroidal, topical treatment option for the millions of Americans living with atopic dermatitis. "The approval of Adquey represents a significant milestone in our commitment to advancing dermatology care," said Ashish Anvekar, President of Acrotech Biopharma Inc. "Patients and clinicians have long sought effective, long-term, non-steroidal treatments that can manage both the inflammation and pruritus associated with eczema. We intend to bring this valuable treatment option to the patients in the U.S. as soon as possible."

Clinical Trial Results

FDA approval was supported by multiple studies including pivotal Phase III controlled trials, which demonstrated that a significantly greater proportion of patients treated with Adquey achieved Investigator’s Global Assessment (IGA) success compared to vehicle (placebo) after four weeks of treatment. The safety profile of Adquey AD was consistent across all three trials. The most common adverse reactions (≥1% and greater than vehicle) was nasopharyngitis. Less common (<1%) adverse reactions in subjects treated with Adquey included application site folliculitis, contact dermatitis, application site rash, and molluscum contagiosum.

https://en.wikipedia.org/wiki/Difamilast

FDA Approves Adquey (difamilast 1%) Ointment for the Treatment of Mild-to-Moderate Atopic Dermatitis

FDA Approves Bysanti (milsaperidone) for the treatment of Bipolar I Disorder and Schizophrenia

Vanda Pharmaceuticals Inc. (Nasdaq: VNDA) today announced that the U.S. Food and Drug Administration (FDA) has approved Bysanti (milsaperidone) tablets, a first line therapy for the acute treatment of manic or mixed episodes associated with bipolar I disorder and for the treatment of schizophrenia in adults.

Bysanti is a new chemical entity (NCE) that belongs in the class of atypical antipsychotics. In clinical studies Bysanti demonstrated bioequivalence to iloperidone across the therapeutic dosing spectrum enabling it to leverage well-established knowledge of efficacy and safety derived from a rich clinical development program and more than 100,000 patient-years of real-world experience with Fanapt® (iloperidone). As such Bysanti represents a novel therapeutic option with a trusted safety profile in the treatment of these serious psychiatric conditions.

"The Bysanti approval marks a significant step forward, offering patients and providers a reliable new treatment grounded in extensive clinical heritage," said Mihael H. Polymeropoulos, M.D., President, CEO and Chairman of the Board of Vanda Pharmaceuticals. "Bysanti exemplifies a new era of accelerated innovation in drug development that can transform how we address unmet needs in behavioral health."

Bysanti is currently being tested as a once-daily adjunctive treatment in treatment-resistant major depressive disorder in an ongoing clinical study expected to complete by the end of this year.

Bysanti (milsaperidone), a new chemical entity, rapidly interconverts to iloperidone, providing dual active molecules that work in tandem by antagonizing dopamine D2, serotonin 5-HT2A, and alpha1-adrenergic receptors to modulate key pathways in these disorders. Its safety profile aligns closely with that established for iloperidone.

Bysanti's unique in-class receptor binding profile, featuring strong alpha-adrenergic binding in excess of dopamine and serotonin receptor binding, makes it suitable for further investigation in conditions that include symptoms of hostility, agitation, and hyperarousal.

https://en.wikipedia.org/wiki/Milsaperidone

FDA Approves Bysanti (milsaperidone) for the treatment of Bipolar I Disorder and Schizophrenia

Caffeine reversed memory problems caused by sleep deprivation

In continuation of my update on Caffeine

Researchers at the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine) have found that caffeine can help restore a specific type of memory that is impaired by sleep deprivation. The findings, published in Neuropsychopharmacology, reveal how caffeine acts on a well-defined brain pathway involved in social memory, the ability to recognize and distinguish people we have encountered before.

The research provides new insight into how sleep loss affects the brain and suggests that caffeine's benefits may extend beyond simply increasing alertness.

How Sleep Loss Affects Social Memory

The study was led by Associate Professor Sreedharan Sajikumar and first author Dr. Lik-Wei Wong from the Department of Physiology and the Healthy Longevity Translational Research Program at NUS Medicine.

The team focused on a part of the brain known as the hippocampal CA2 region. The hippocampus is critical for learning and memory, while the CA2 area plays a particularly important role in forming social memories. This brain region also receives signals involved in regulating sleep and wakefulness.

To investigate the effects of sleep deprivation, the researchers subjected laboratory animals to five hours of sleep loss. Afterward, caffeine was provided in drinking water for unrestricted consumption over a seven-day period.

Caffeine Restored Brain Communication

Caffeine is a stimulant that blocks adenosine receptor signaling pathways. Adenosine accumulates during periods of wakefulness and helps reduce brain activity, contributing to feelings of sleepiness.

The researchers then performed electrophysiological recordings on hippocampal tissue samples to assess synaptic plasticity, the brain's ability to strengthen or weaken connections between nerve cells in response to experience and learning.

The results showed that sleep deprivation disrupted the maintenance of synaptic plasticity in the CA2 region. Communication between neurons weakened, reducing the brain's capacity to strengthen important neural connections. These changes were accompanied by noticeable deficits in social recognition memory.

Overall, the findings demonstrated that sleep loss impaired both brain function and behavior through a specific neural circuit.

A Targeted Effect on Memory Circuits

The researchers also found that caffeine administered before sleep deprivation restored synaptic communication in the CA2 region and returned plasticity to normal levels.

As a result, the social memory deficits caused by sleep loss were reversed. Importantly, caffeine's effects were highly selective. Rather than broadly increasing activity throughout the brain, it specifically restored the disrupted pathway linked to social memory.

This targeted action meant that animals in the control group that had not experienced sleep deprivation did not show signs of excessive neural stimulation despite receiving caffeine.

"Sleep deprivation does not just make you tired. It selectively disrupts important memory circuits," noted Dr. Wong. "We found that caffeine can reverse these disruptions at both the molecular and behavioral levels. Its ability to do so suggests that caffeine's benefits may extend beyond simply helping us stay awake."

Assoc Prof Sajikumar added, "Our findings position the CA2 region as a critical hub linking sleep and social memory. This research enhances our understanding towards the biological mechanisms underlying sleep-related cognitive decline. This could inform future approaches to preserving cognitive performance."

Implications for Brain Health and Future Research

The findings highlight the essential role sleep plays in maintaining healthy cognition and memory. By showing that caffeine can restore specific neural pathways affected by sleep deprivation, the study provides new insight into potential targeted approaches for addressing cognitive decline.

The researchers plan to continue investigating how caffeine influences memory consolidation and memory retrieval. Future studies will also use targeted manipulations of brain circuits to better understand the causal relationship between neural pathways and memory function.

https://en.wikipedia.org/wiki/Caffeine

Caffeine reversed memory problems caused by sleep deprivation  

FDA Approves Desmoda (desmopressin acetate) Oral Solution for Central Diabetes Insipidus

In continuation of my update on Desmoda

Eton Pharmaceuticals, Inc (“Eton” or “the Company”) (Nasdaq: ETON), an innovative pharmaceutical company focused on developing and commercializing treatments for rare diseases, today announced the U.S. Food and Drug Administration (FDA) approval of a New Drug Application (NDA) for Desmoda™ (desmopressin acetate) Oral Solution for the management of central diabetes insipidus, also known as arginine vasopressin deficiency (AVP-D), as antidiuretic replacement therapy for patients of all ages.

Desmoda is the first and only FDA-approved desmopressin oral solution

Commercial launch expected on March 9, 2026

Desmoda eliminates tablet splitting and crushing, enabling precise, individualized dosing for patients of all ages

The product is expected to be a significant long-term growth contributor, with potential peak sales of $30-50 million annually and patent protection extending through 2044

Desmoda is the first and only FDA-approved oral liquid formulation of desmopressin, developed to support precise, individualized dosing in a disease where careful titration is essential to maintaining water balance. Desmoda is supplied as a ready-to-use oral solution (0.05 mg/mL) that does not require tablet splitting, crushing, refrigeration, mixing, or shaking.

Eton estimates that there are more than 13,000 patients with central diabetes insipidus in the U.S., including approximately 3,000-4,000 pediatric patients. The company expects product peak sales of $30-50 million annually.

“Desmoda represents one of the most important product launches in Eton’s history. It builds on our strategy of delivering differentiated therapies to rare endocrine patients. By leveraging our existing pediatric endocrinology platform, we believe Desmoda has the potential to become a foundational therapy in this category,” said Sean Brynjelsen, Chief Executive Officer of Eton Pharmaceuticals. “In central diabetes insipidus, effective long-term management depends on accurately matching desmopressin dosing to each patient’s diurnal pattern of water balance. Historically, clinicians have primarily relied on formulations that were not designed for fine dose adjustments or had other administration issues, and both clinicians and families often had to rely on workarounds. Desmoda introduces a liquid solution designed to deliver individualized dosing precision and consistency for patients across the age spectrum.”

Central diabetes insipidus is a rare, but serious condition caused by inadequate production of the hormone vasopressin from the hypothalamus/posterior pituitary. Treatment with desmopressin is the standard of care, but dosing must be individualized to avoid complications related to over- or under-treatment. Oral liquid dosing allows clinicians to incrementally fine-tune therapy and adjust dosing over time as clinical needs evolve.

“Central diabetes insipidus requires careful, individualized management, where dosing precision and flexibility truly matter. Having a liquid formulation of desmopressin has the potential to meaningfully support how we initiate and manage therapy. It’s encouraging to see innovation that directly addresses real-world challenges faced by clinicians and families and gives greater confidence when tailoring treatment across age groups,” said Dr. Lewis Blevins, Director of the California Center for Pituitary Disorders and Professor of Medicine and Neurological Surgery at the University of California, San Francisco.

“For families living with central diabetes insipidus/AVP-D, treatment demands precision, consistency, and careful management of dosing. A liquid option like Desmoda is a meaningful improvement because it helps make sure that the dose is always right, every time. This is very important in cases where the wrong dose can have a big impact," said Muriël Marks, board member of Worldwide Adrenal and Pituitary Organizations (‘WAPO’).

Desmoda will be promoted by Eton’s existing team of pediatric endocrinology rare disease specialists which currently promotes ALKINDI SPRINKLE® (hydrocortisone), KHINDIVITM (hydrocortisone), and INCRELEX® (mecasermin). Desmoda is expected to be available on March 9th exclusively through Anovo, a specialty pharmacy dedicated to serving patients with rare and chronic conditions. Anovo will administer the Eton Cares Program in partnership with Eton Pharmaceuticals. The program provides prescription fulfillment, insurance benefits investigation, educational support, financial assistance for qualified patients, and other services designed to help patients access treatment. Eton Cares will offer co-pay assistance to allow for $0 co-pay for qualifying patients.

https://en.wikipedia.org/wiki/Desmopressin

FDA Approves Desmoda (desmopressin acetate) Oral Solution for Central Diabetes Insipidus

FDA Grants Accelerated Approval to Yuviwel (navepegritide) for Children with Achondroplasia

Ascendis Pharma A/S (Nasdaq: ASND) today announced that the U.S. Food & Drug Administration (FDA) has granted approval under the FDA’s Accelerated Approval Program for Yuviwel (navepegritide; developed as TransCon® CNP), the first and only once-weekly treatment indicated to increase linear growth in children 2 years of age and older with achondroplasia with open epiphyses and the only one to provide continuous systemic exposure to CNP over the weekly dosing interval. Continued approval for this indication, which was based on an improvement in annualized growth velocity (AGV), may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

• The first and only approved achondroplasia therapy to provide continuous systemic exposure to CNP over the weekly dosing interval
• Commercial availability expected during early part of Q2 2026
• Rare Pediatric Disease Priority Review Voucher granted in connection with approval

Achondroplasia is a rare genetic condition causing skeletal dysplasia and, for many affected individuals, an increased risk of muscular, neurological, and cardiorespiratory complications. Yuviwel is a prodrug of C-type natriuretic peptide (CNP) administered once weekly, designed to provide continuous exposure of active CNP to receptors on tissues throughout the body to counteract the overactive FGFR3 signaling in achondroplasia.

“The approval of once-weekly Yuviwel is a major step forward in the treatment of children with achondroplasia, giving physicians for the first time the option of prescribing a once-weekly medicine backed by compelling efficacy and excellent tolerability data from three randomized, double-blind, placebo-controlled clinical trials,” said Carlos A. Bacino, MD, FACMG, Professor of Molecular and Human Genetics, Baylor College of Medicine and Texas Children’s Hospital. “My goal is to help children and parents develop care plans tailored to their individual needs and objectives, and I look forward to adding Yuviwel to my discussions with them.”

“Little People of America, the largest national advocacy and support organization for people with dwarfism, is committed to ensuring that the voices of people with dwarfism remain central in conversations about research and medical options such as Yuviwel,” said the Board of Directors of Little People of America. “We champion dwarf and disability pride, advocate for inclusion and respect, and foster open dialogue across diverse perspectives. Our goal is to empower individuals and families to make healthcare decisions that reflect their own values and experiences, while pushing for research efforts and new treatment options such as this that could have the potential to support outcomes that truly matter to our community.”

The FDA based its approval of Yuviwel on their review of the clinical package for TransCon CNP submitted with the Company’s New Drug Application, which included safety and efficacy data from three randomized, double-blind, placebo-controlled clinical trials and up to three years of open-label extension data. The pivotal ApproaCH Trial data is available in JAMA Pediatrics.i

“We are confident in Yuviwel’s potential to transform the treatment of achondroplasia and are deeply grateful to patients, clinicians, and advocates for their many contributions to this important milestone,” said Jan Mikkelsen, President and Chief Executive Officer at Ascendis Pharma. “We have listened to advocacy groups for people with dwarfism to ensure we address what the community actually cares about. This reflects our ongoing commitment to pursue outcomes that patient communities have told us are important to them, and gives the achondroplasia community a new way to look at the promise of pharmacological treatment options.”

Ascendis expects to make Yuviwel available through prescribing physicians in the United States during the early part of the second quarter of 2026. Ascendis plans to offer a suite of patient services for Yuviwel through its U.S. Ascendis Signature Access Program (A.S.A.P.), including support navigating the treatment journey and financial assistance programs for eligible patients.

With this approval, the FDA also issued a Rare Pediatric Disease Priority Review Voucher (PRV), which confers priority review to a subsequent drug application that would not otherwise qualify for priority review. This program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases.

FDA Grants Accelerated Approval to Yuviwel (navepegritide) for Children with Achondroplasia

FDA Approves Icotyde (icotrokinra) for the Treatment of Plaque Psoriasis

Johnson & Johnson (NYSE: JNJ) announced today that the U.S. Food and Drug Administration (FDA) has approved Icotyde (icotrokinra), an interleukin-23 (IL-23) receptor antagonist for the treatment of moderate-to-severe plaque psoriasis in adults and pediatric patients 12 years of age and older who weigh at least 40 kg who are candidates for systemic therapy or phototherapy. Icotyde is the first and only targeted oral peptide that precisely blocks the IL-23 receptor.

• Johnson & Johnson introduces the first and only IL-23R targeted oral peptide that delivers complete skin clearance and favorable safety profile in a once-daily pill
• Icotyde offers an innovative new option for patients with moderate-to-severe plaque psoriasis to address patients cycling on topical therapies in need of systemic treatment

“Icotyde delivers something unique in psoriasis treatment – combining skin clearance with a favorable safety profile in a once‑daily pill, making it an easy addition to a patient’s routine,” said Linda Stein Gold, M.D., Director of Dermatology Clinical Research at Henry Ford Health.a “With new guidance from the International Psoriasis Council that clarifies when to move beyond cycling on topical treatments to systemic therapy, an innovative option like Icotyde is a potential game‑changer for many adult and adolescent patients.”

Clinical evidence summary

Icotyde met all primary efficacy endpoints and demonstrated a favorable safety profile across four Phase 3 studies including 2,500 patients. The approval is based on an unprecedented body of evidence from the ICONIC clinical development program, which simultaneously evaluated Icotyde in adults and adolescents, high impact sites such as scalp and genital PsO, and in duplicate head-to-head trials versus an active comparator. In the head-to-head superiority studies, approximately 70% of patients achieved clear or almost clear skin (IGA 0/1) and 55% of patients achieved a Psoriasis Area and Severity Index (PASI) 90 response at Week 16.3,b,c Rates of adverse reactions for Icotyde treated patients were within 1.1% of placebo through Week 16 and no new safety signals were identified through Week 52.

“With the FDA approval of Icotyde, Johnson & Johnson is setting a new standard for the treatment of moderate-to-severe plaque psoriasis,” said Jennifer Taubert, Executive Vice President, Worldwide Chairman, Innovative Medicine, Johnson & Johnson. “We’re proud to bring this game-changing innovation to the market, marking a transformative shift in plaque psoriasis management that empowers patients and clinicians to reach their treatment goals.

Unmet need in moderate-to-severe plaque psoriasis

Psoriasis affects more than 8 million Americans, impacting physical comfort and quality of life, especially when lesions are on visible or sensitive areas.5 For many with moderate-to-severe disease, targeted systemic treatments are key. This aligns with International Psoriasis Council guidance to transition to systemic therapy if two cycles of topical medications applied for four weeks fail to bring meaningful improvement.

“Finding the right treatment can take time, during which people with psoriatic disease should be considering multiple factors from efficacy to safety to how the treatment fits into their everyday life,” said Leah M. Howard, J.D., President and CEO of the National Psoriasis Foundation.d “The approval of a novel systemic therapy changes the conversation about treatment options for our community.”

“The approval of Icotyde represents a pivotal moment for people with plaque psoriasis,” said John Reed, M.D., Ph.D., Executive Vice President, R&D, Innovative Medicine, Johnson & Johnson. “At Johnson & Johnson, we are harnessing our scientific expertise to transform cutting-edge science into meaningful solutions for patients. Icotyde is a fundamentally different treatment with the potential to redefine what physicians and patients can expect from psoriasis treatment. 

https://en.wikipedia.org/wiki/Icotrokinra

FDA Approves Icotyde (icotrokinra) for the Treatment of Plaque Psoriasis

FDA Approves Lynavoy (linerixibat) for Cholestatic Pruritus in Patients with Primary Biliary Cholangitis

GSK  announced   the US Food and Drug Administration (FDA)  approval of  Lynavoy (linerixibat) for the treatment of cholestatic pruritus in adult patients with PBC. Lynavoy, an ileal bile acid transporter (IBAT) inhibitor that reduces multiple drivers of chronic itch, is the first medicine approved in the US for this indication.5

Lynavoy, an ileal bile acid transporter (IBAT) inhibitor, is the first medicine approved in the US for the treatment of cholestatic pruritus in patients with PBC

Up to 89% of people living with PBC experience cholestatic pruritus, an internal itch with a debilitating impact on quality of life1-4

Approval based on the positive GLISTEN phase III trial with regulatory reviews underway in the EU, UK, Canada and China

GSK previously announced on 9 March a licence agreement under which Alfasigma S.p.A. will acquire worldwide exclusive rights to develop, manufacture and commercialise linerixibat. This transaction is ongoing and is subject to customary conditions, including applicable regulatory agency clearances such as under the Hart-Scott-Rodino Act in the US.

Cholestatic pruritus is an internal itch experienced by up to 89% of people living with PBC, a rare autoimmune disease that can lead to liver failure.1-4 It is a serious condition that can be debilitating, with patients experiencing sleep disturbance, fatigue, impaired quality of life and even sometimes requiring liver transplantation in the absence of liver failure

https://en.wikipedia.org/wiki/Linerixibat

FDA Approves Lynavoy (linerixibat) for Cholestatic Pruritus in Patients with Primary Biliary Cholangitis

FDA Approves Lifyorli (relacorilant) Plus Nab-Paclitaxel for the Treatment of Patients with Platinum-Resistant Ovarian Cancer

In continuation of my update on relacorilant

Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, announced  the U.S. Food and Drug Administration  approval of Lifyorli (relacorilant) in combination with nab-paclitaxel for the treatment of adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens, at least one of which included bevacizumab. Lifyorli is the first FDA-approved selective glucocorticoid receptor antagonist (SGRA).

Approval was based on the positive outcomes of Lifyorli's pivotal ROSELLA trial, which enrolled 381 patients with platinum-resistant ovarian cancer who had received one to three prior lines of therapy, at least one of which included bevacizumab. Patients were randomized 1:1 to receive either Lifyorli plus nab-paclitaxel or nab-paclitaxel monotherapy. No biomarker selection was required.

ROSELLA met its dual primary endpoints of progression-free and overall survival. Patients treated with Lifyorli in addition to nab-paclitaxel experienced a 35 percent reduction in the risk of death compared to patients treated with nab-paclitaxel alone (hazard ratio: 0.65; p-value: 0.0004), with a median overall survival (OS) of 16.0 months, compared to 11.9 months for patients receiving nab-paclitaxel alone, a difference of 4.1 months. Patients who received Lifyorli in addition to nab-paclitaxel also experienced a 30 percent reduction in the risk of disease progression (hazard ratio: 0.70; p-value: 0.008), as assessed by blinded independent central review (PFS-BICR), compared to patients treated with nab-paclitaxel alone.

The combination of Lifyorli with nab-paclitaxel was well-tolerated and manageable. The safety of Lifyorli was assessed in a pooled analysis of patients from ROSELLA and Lifyorli's Phase 2 trial. The prescribing information for Lifyorli includes warnings and precautions for neutropenia and severe infections, adrenal insufficiency, exacerbation of conditions treated with glucocorticoids and embryo-fetal toxicity. The most common adverse reactions experienced by more than 20 percent of patients (including laboratory abnormalities) were decreased hemoglobin, decreased neutrophils, fatigue, nausea, diarrhea, decreased platelets, rash and decreased appetite.

Data from ROSELLA were first presented at ASCO 2025 (American Society of Clinical Oncology) with simultaneous publication in The Lancet. Complete results from ROSELLA will be presented at the Society of Gynecologic Oncology (SGO) meeting in April.

"Data demonstrate that Lifyorli plus nab-paclitaxel provides a clinically meaningful benefit in overall survival for patients with platinum-resistant ovarian cancer and is well tolerated. Lifyorli is positioned to become a new standard-of-care treatment," said Rob Coleman, M.D., Texas Oncology and special advisor to the president of the GOG Foundation. "Having a new treatment for this advanced, recurrent disease will provide clinicians with a compelling option to help patients with this extremely difficult-to-treat cancer."

"The FDA's approval of Lifyorli in combination with nab-paclitaxel is welcome news to all of us in the ovarian cancer community," said Sarah DeFeo, Chief Program Officer at Ovarian Cancer Research Alliance (OCRA). "We are grateful to everyone who participated in the clinical trials, their families and the physicians who helped advance this urgently needed treatment option for patients with platinum-resistant ovarian cancer."

https://en.wikipedia.org/wiki/Relacorilant

More: 

FDA Approves Lifyorli (relacorilant) Plus Nab-Paclitaxel for the Treatment of Patients with Platinum-Resistant Ovarian Cancer

How a cheap, century-old drug can improve life with type 1 diabetes

In continuation of my update on Metformin

A Garvan-led clinical trial has found that using a common and inexpensive type 2 diabetes drug reduces insulin needs in type 1 diabetes, opening doors for improved management of the condition.

For years, doctors have prescribed metformin, an old but common type 2 diabetes medication, to treat insulin resistance in type 1 diabetes. This has been largely based on anecdotal evidence. Now, a clinical trial led by the Garvan Institute of Medical Research has found that metformin does not counteract insulin resistance in type 1 diabetes, but instead reduces the amount of insulin needed to maintain blood sugar levels in the ideal range.

Published in Nature Communications, these surprising findings could improve how doctors manage type 1 diabetes and ease the significant burden that people with the condition face when using insulin alone.

Can we overcome insulin resistance in type 1 diabetes?

Type 1 diabetes is an autoimmune condition affecting over 130,000 Australians in which the immune system incorrectly attacks the insulin-producing cells of the pancreas. As a result, people with type 1 diabetes need to administer insulin for the rest of their lives to regulate their blood sugar levels. Managing blood sugar levels with insulin is not easy. In fact, it is estimated that people living with type 1 diabetes have to make 180 extra decisions per day related to their diabetes management.

In some people with type 1 diabetes, long-term insulin use can lead to insulin resistance, where the body's cells no longer respond effectively to the drug. This means that people need ever-increasing amounts of insulin to keep blood sugar levels under control.

"Insulin resistance is a growing problem in type 1 diabetes. Not only does it make regulating blood sugar levels difficult, but it is an underappreciated risk factor for heart disease, which is one of the biggest causes of health complications and deaths in those with type 1 diabetes," says Dr. Jennifer Snaith, endocrinologist and co-lead of the study.

To address this, a Garvan team led by Dr. Snaith and Professor Jerry Greenfield undertook the world's first randomized controlled trial in adults testing whether metformin, a cheap, oral drug normally used to counteract insulin resistance in type 2 diabetes, could do the same in type 1 diabetes. It is estimated that the drug is currently used off-label by up to 13,000 Australians with type 1 diabetes, but it remains unclear how exactly it works. This trial was called the Insulin Resistance in type 1 Diabetes Managed with Metformin (INTIMET) study.

"We randomized 40 adults with long-term type 1 diabetes to take either metformin or a placebo for six months. We examined whether their insulin resistance changed over that time through a sophisticated and comprehensive research technique, called a clamp study, that allowed us to map insulin resistance in different parts of the body," explains Professor Greenfield.

A surprise finding challenges assumption of metformin action

Unexpectedly, the team found that the use of metformin did not lead to improvements in insulin resistance or changes to blood sugar levels. This suggests that, unlike with type 2 diabetes, metformin does not work to counter insulin resistance in type 1 diabetes. However, metformin did decrease the amount of insulin people needed to keep their blood sugars stable.

"Although we didn't find changes to insulin resistance from the use of metformin, we did show that people taking it used around 12% less insulin than those on placebo. This is an important result. Insulin is a relatively old treatment which, while lifesaving, comes with significant mental and physical burden.

"This means that lowering the amount of insulin used is a priority for many people living with type 1 diabetes. We have shown that a very cheap, accessible medication may serve this purpose and this is very exciting," Dr. Snaith says.

A role for gut microbes?

The team is now investigating how metformin may work to lower the amount of insulin needed by those with type 1 diabetes.

Professor Greenfield explains, "Metformin has been available in various forms for around 100 years, but its mechanism of action remains unknown. We would have expected that the observed reductions in insulin dose induced by metformin in our study would be due to the body becoming more sensitive to insulin, that is, becoming less insulin resistant. But we have shown that is not the case. Our priority is now working out how metformin is achieving this effect."

"There is increasing evidence suggesting that metformin may act on the gut. This is why we are now investigating how metformin changes gut flora, also known as the microbiome, in people with type 1 diabetes. This has not been studied before in type 1 diabetes. We're hoping this will provide clues on metformin's mechanism of action, so that it can be more widely used in the management of type 1 diabetes," adds Dr. Snaith.

How a cheap, century-old drug can improve life with type 1 diabetes

Synthetic stress hormone dexamethasone could reduce certain breast cancer metastases

The drug dexamethasone supplements cancer treatments to alleviate side effects of chemotherapy such as nausea or inflammation. Researchers at the University of Basel, Switzerland, have now discovered that it also fights metastases in certain types of breast cancer.

The active substance dexamethasone is a synthetic signaling substance with a similar effect to the body's own stress hormone cortisol. A research group at the University of Basel has found evidence that this drug, which has been in use for a long time, could have a new, additional effect on certain treatment-resistant breast cancers.

Breast cancer of the "estrogen receptor-positive" (ER+ for short) subtype can usually be treated with anti-hormonal therapy. The target of this therapy is the estrogen receptor, which is hyperactive in these tumors and drives abnormal cell division. Hormone therapy uses drugs that deactivate or break down the estrogen receptor, thereby slowing the growth of cancer cells. However, this type of tumor sometimes forms metastases that no longer respond to hormone therapy.

Fewer metastases

A research team led by Professor Mohamed Bentires-Alj from the Department of Biomedicine at the University of Basel and the University Hospital Basel reports in the journal EMBO Molecular Medicine that dexamethasone can combat precisely these therapy-resistant metastases. In trials with mice with therapy-resistant ER+ tumors, dexamethasone reduced liver metastases and prolonged the animals' survival.

Further analyses provided more detailed insights into how the drug achieves this effect: dexamethasone activates the glucocorticoid receptor. This, in turn, suppresses the production of the estrogen receptor. "As a result, the cancer cells lose the main driver of tumor growth," explains Dr. Madhuri Manivannan, lead author of the study.

In addition to the trials with mice, the researchers also used patient-derived tumor tissue grown in the laboratory known as organoids. Here, they also observed that the amount of estrogen receptor decreased with the addition of dexamethasone

https://en.wikipedia.org/wiki/Dexamethasone

Synthetic stress hormone dexamethasone could reduce certain breast cancer metastases

Praxis Precision Medicines Announces FDA Acceptance and Priority Review of New Drug Application for Relutrigine in Patients with SCN2A and SCN8A DEEs

Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a fully integrated, leading central nervous system (CNS) precision neuroscience biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review its New Drug Application (NDA) for relutrigine, for the treatment of SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs). The FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of September 27, 2026.

• FDA assigned PDUFA target action date of September 27, 2026

“Our first FDA acceptance of an NDA submission marks a significant milestone in our evolution to a commercial-stage company and an important step toward delivering innovative, precision neuroscience therapies to patients in need. SCN2A/8A DEEs have no currently approved targeted therapies and relutrigine, if approved, would be the first disease-modifying therapy for children suffering from these devastating and fatal conditions. We look forward to working closely with the FDA during the review process while continuing to advance our launch preparations,” said Marcio Souza, president and chief executive officer.

Relutrigine for treatment of SCN2A/8A DEEs

The NDA is supported by positive results from the EMBOLD study, which was stopped early for efficacy following a successful interim analysis and recommendation from the Data Monitoring Committee. Relutrigine has an Orphan Drug Designation, as well as a Rare Pediatric Disease Designation and a Breakthrough Therapy Designation. If granted approval, relutrigine will be the first FDA-approved therapy for SCN2A/8A DEE as well as be eligible for a Pediatric Review Voucher.

Relutrigine is also being investigated in broad DEEs through the EMERALD trial, which is expected to be completed by the end of 2026.

About Relutrigine

Relutrigine is a first-in-class small molecule in development for the treatment of developmental and epileptic encephalopathies (DEEs) as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in severe DEEs. Relutrigine’s mechanism of precision sodium channel (NaV) modulation is consistent with superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of relutrigine have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. Relutrigine has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel modulation. Data from cohort 1 of the Phase 2 EMBOLD study demonstrated a well-tolerated, robust, short- and long-term improvement in motor seizures in a heavily pre-treated population, alongside maintained seizure freedom in some patients with SCN2A- and SCN8A-DEE. Relutrigine has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation from the FDA for the treatment of SCN2A-DEE, SCN8A-DEE and Dravet syndrome; as well as Breakthrough Therapy Designation (BTD), and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE.

Praxis Precision Medicines Announces FDA Acceptance and Priority Review of New Drug Application for Relutrigine in Patients with SCN2A and SCN8A DEEs

Elevar Therapeutics Announces FDA Acceptance for Review of New Drug Application for Lirafugratinib as Second-line Cholangiocarcinoma Treatment

Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd. and a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, today announced that the U.S. Food and Drug Administration (FDA) has completed its filing review of the New Drug Application (NDA) for lirafugratinib, an investigational therapy, for the treatment of patients with cholangiocarcinoma (CCA) with FGFR2 fusions or rearrangements who have received prior therapy. The FDA determined that the NDA is sufficiently complete to permit a substantive review and granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) target action date of September 27, 2026.

• With Priority Review designation, FDA set a Sept. 27 PDUFA date for approval decision
• Lirafugratinib achieved a 46.5% ORR, in CCA patients with FGFR2 fusion and rearrangement

Priority Review designations are given to applications for medicines that, if approved, would lead to “significant improvements in the safety or effectiveness of the treatment” of a serious condition, according to the FDA. The Priority Review designation of the lirafugratinib NDA was supported by positive clinical data from the Phase 1/2 ReFocus trial (NCT04526106), which demonstrated a confirmed objective response rate (ORR) of 46.5% in the patients with the proposed indication. Its safety profile in the clinical data has been shown to be predictable and manageable through dose adjustments.

“Lirafugratinib has established a compelling clinical profile that differentiates it from existing treatment options,” said Dong-Gun Kim, chief executive officer of Elevar. “We are very pleased with the FDA’s priority review designation and focused on advancing the review process efficiently to bring this therapy to patients as quickly as possible.”

CCA, also known as bile duct cancer, is rare, with about 8,000 people in the U.S. diagnosed each year, according to the American Cancer Society.

Elevar Therapeutics continues to evaluate lirafugratinib in ongoing clinical development programs, including studies in other FGFR2-altered solid tumors. Any future indications will be subject to regulatory review and approval.

For more information about lirafugratinib, visit ElevarTX.com.

About Lirafugratinib

Lirafugratinib (RLY-4008) is a potent, selective, and oral small molecule inhibitor of FGFR2, a receptor tyrosine kinase that is frequently altered in certain cancers. FGFR2 is one of four members of the FGFR family, a set of closely related proteins with highly similar protein sequences and properties. Preclinically, lirafugratinib demonstrated FGFR2-dependent killing in cancer cell lines and induced regression in in vivo models with minimal inhibition of other targets, including other members of the FGFR family. In addition, lirafugratinib demonstrated strong activity against known clinical on-target resistance mutations in vitro and in vivo preclinical models. Lirafugratinib is currently being evaluated in a clinical trial to enroll additional patients with previously treated, advanced or metastatic solid tumors other than CCA harboring FGFR2 fusion or rearrangement, who have not been treated with prior FGFR inhibitors.

Elevar Therapeutics Announces FDA Acceptance for Review of New Drug Application for Lirafugratinib as Second-line Cholangiocarcinoma Treatment

How statins harm muscles—and how to stop it

In continuation of my update  on statin 

Statins have transformed heart health, saving millions of lives by lowering cholesterol and reducing the risk of heart attacks and strokes. But for many patients, these drugs come with a troubling downside: muscle pain, weakness and, in rare cases, severe muscle breakdown that can lead to kidney failure.

University of British Columbia researchers and their collaborators at the University of Wisconsin-Madison have now pinpointed the cause. Their findings, published last week in Nature Communications, could pave the way for a new generation of statins without these side effects.

How statins affect muscle cells

The team used cryo-electron microscopy, a powerful imaging technique that reveals proteins at near-atomic detail, to capture how statins interact with a critical muscle protein called the ryanodine receptor (RyR1). This protein acts like a gatekeeper for calcium inside muscle cells, opening only when muscles need to contract. When statins bind to it, they force the gate open, causing calcium to leak continuously—a toxic effect that can damage muscle tissue.

"We were able to see, almost atom by atom, how statins latch onto this channel," said lead author Dr. Steven Molinarolo, a postdoctoral researcher in UBC's department of biochemistry and molecular biology. "That leak of calcium explains why some patients experience muscle pain or, in extreme cases, life-threatening complications."

Implications for future statin development

The study focused on atorvastatin, one of the most widely prescribed statins, but the findings suggest the effect may be common across the drug class. The researchers discovered that statins bind in a highly unusual way: Three molecules cluster together inside a pocket of the protein. The first molecule attaches when the channel is closed, priming it to open. Two more molecules then wedge in, forcing the channel wide open.

"This is the first time we've had a clear picture of how statins activate this channel," said Dr. Filip Van Petegem, senior author and professor at UBC's Life Sciences Institute. "It's a big step forward because it gives us a roadmap for designing statins that don't interact with muscle tissue."

By adjusting only those parts of the statin molecule that are responsible for the negative effects, scientists could preserve the part that lowers cholesterol while reducing the risk.

https://en.wikipedia.org/wiki/Statin

How statins harm muscles—and how to stop it

Methamphetamine impairs dopamine uptake by targeting a protein modification

In continuation of my update on Methamphetamine

Dopamine brings on a surge of pleasure, but too much dopamine in a synapse can ultimately lead to mood disorders and addiction. A recent preclinical study published in The FASEB Journal suggests that methamphetamine boosts dopamine levels by reversibly reducing the amount of a modification on the dopamine transporter. Loss of the modification decreases the transporter's ability to remove the neurotransmitter from synapses.

The findings shed new light on how the transporter works and could help researchers develop new treatments for addiction and neurological disorders, such as depression and schizophrenia.

The neurotransmitter dopamine is involved in many processes, such as movement, reward, motivation, learning, and memory. When triggered, special neurons in the brain release dopamine into the gaps between neurons, called synapses, making a person experience happiness and euphoria. Low levels, however, can make a person feel depressed.

Because inappropriate amounts can lead to psychological disorders or addiction, levels of the neurotransmitter are regulated by dopamine transporters (DATs) that remove excess dopamine from synapses. Protein modifications can modulate DAT activity. Palmitoylation enhances DAT reuptake of dopamine, whereas phosphorylation by the enzyme protein kinase C decreases reuptake.

Methamphetamine can slow reuptake by stimulating phosphorylation, but Roxanne Vaughan, James Foster, and colleagues at the University of North Dakota wanted to see whether the drug also affects DAT palmitoylation.

In a rat model and in in vitro experiments, methamphetamine rapidly reduced DAT palmitoylation and DAT transporter activity. Palmitoylation returned to normal levels much more quickly than transporter activity, which suggests that additional processes are involved in keeping DAT activity suppressed after palmitoylation recovers.

The methamphetamine effects were specific—cocaine did not impact palmitoylation. In vitro experiments revealed that protein kinase C was necessary for the reduction in palmitoylation. Additional experiments with DAT mutated at a position where half of the palmitoylation typically occurs reduced palmitoylation to about half of wild-type levels, and the mutant took up even less dopamine in methamphetamine-treated cells.

"By revealing that methamphetamine suppresses dopamine transporter palmitoylation, this study identifies a previously unknown mechanism through which the drug alters dopamine signaling," says Vaughan. "Understanding this process could guide the development of treatments aimed at stabilizing or restoring transporter regulation, potentially reducing the long-term dopamine imbalances and neurochemical damage linked to methamphetamine addiction."

https://en.wikipedia.org/wiki/Methamphetamine

Methamphetamine impairs dopamine uptake by targeting a protein modification

Polyphenol-rich diets associated with lower long-term cardiovascular disease risk

In continuation of my update on Polyphenol-rich diets

 People who regularly consume polyphenol-rich foods and drinks, such as tea, coffee, berries, cocoa, nuts, whole grains and olive oil, may have better long-term heart health

The research, led by King's College London, found that those with higher adherence to polyphenol-rich dietary patterns had lower predicted cardiovascular disease (CVD) risk.

Polyphenols are natural compounds found in plants that are linked to various health benefits, including improved heart, brain, and gut health.

The study, published today in BMC Medicine, followed more than 3,100 adults from the TwinsUK cohort for over a decade, found that diets rich in specific groups of polyphenols were linked to healthier blood pressure and cholesterol profiles, contributing to lower CVD risk scores.

For the first time, the researchers also analyzed a large number of metabolites in the urine that are produced when the body breaks down polyphenols.

These biomarkers confirmed that individuals with higher levels of polyphenol metabolites—especially those derived from specific groups of polyphenols, flavonoids and phenolic acids—had lower cardiovascular risk scores. They also had increased HDL cholesterol, also know as "good" cholesterol.

The study used a newly developed polyphenol dietary score (PPS) to capture intake of 20 key polyphenol-rich foods commonly consumed in the U.K., ranging from tea and coffee to berries, olive oil, nuts, and whole grains.

This score showed stronger associations with cardiovascular health than estimates of total polyphenol intake, likely because it captures overall dietary patterns rather than individual compounds. This finding suggests that considering the whole diet provides a more accurate picture of how polyphenol-rich foods work together to support long-term heart health

Professor Ana Rodriguez-Mateos, senior author and Professor of Human Nutrition at King's College London, said, "Our findings show that long-term adherence to polyphenol-rich diets can substantially slow the rise in cardiovascular risk as people age. Even small, sustained shifts towards foods like berries, tea, coffee, nuts, and whole grains may help protect the heart over time."

Dr. Yong Li, first author of the study, added, "This research provides strong evidence that regularly including polyphenol-rich foods in your diet is a simple and effective way to support heart health. These plant compounds are widely available in everyday foods, making this a practical strategy for most people."

The researchers note that while cardiovascular risk naturally increases with age, higher polyphenol intake was associated with a slower progression of risk over the 11-year follow-up period. They also emphasize the need for future dietary intervention studies to further validate these associations.

Polyphenol-rich diets associated with lower long-term cardiovascular disease risk